A middle ear effusion (MEE) is a collection of fluid within the middle ear, and is indicative and characteristic of inflammation in the ear. An effusion commonly results from the blockage, constriction, or dysfunction of the Eustachian tube commonly associated with otitis media (OM), or middle-ear infection. This dysfunction causes negative pressure to develop in the middle ear cavity, which draws out fluid from the surrounding middle ear and mastoid tissue. At least 75% of children under 3 years of age have experienced some form of OM and MEE, as discussed by Ramakrishnan et al., “Diagnosis and treatment of otitis media,” Am. Family Physician, vol. 76, pp. 1650-58, (2007), which is incorporated herein by reference. Depending on the infectious conditions of the ear and the immune response of the body, MEEs can become increasingly purulent and mucous-filled. Typically, MEEs can persist for weeks or months, and can eventually lead to the formation of a “glue ear,” or a thick, mucoid effusion. The altered viscosity of a MEE prevents efficient clearance by middle-ear cilia, and likely is related to repeated episodes of OM.
It is therefore critical to accurately diagnose and characterize the many different presentations of OM, including MEEs, to ensure that appropriate and sufficient treatment is provided to the patient. Generally, MEEs may be serous or mucoid, can eventually become purulent, and may present a host of other OM related symptoms (e.g. injection, inflammation, or pain). Clinically, MEEs can cause varying degrees of hearing loss in the short term. In the long term, MEEs can cause even more serious complications such as structural damage to finer structures in the middle ear, and speech or learning delays if left untreated. Prescribing an effective treatment for MEEs is difficult, as antibiotics may not immediately clear an effusion, and surgery may be an unnecessary risk if there is not sufficient cause for concern (e.g. hearing loss, speech delay, damage to middle ear bones, persistence for longer than 3-6 months, etc.). However, the persistence and prevalence of OM is the reason why it is one of the most common surgically treated conditions in children under anesthesia.
The presence and the degree of severity of a MEE is not always clear when observed with standard otoscopic methods, which is why pneumatic otoscopy is often cited as the “gold-standard” to assess the presence of MEEs, although rarely performed in practice. Tympanometry and acoustic reflectometry techniques are also useful to help identify MEEs, but are recommended to be compared alongside pneumatic otoscopy results. Tympanocentesis, the removal of a MEE by aspiration through a needle, can be performed to remove and directly examine a MEE, but it is rarely performed in most primary care clinics as it is considered an invasive procedure that carries additional risk to the patient. Ultrasound-based methods lack the spatial resolution to accurately resolve middle ear biofilms, and typically require unobstructed water-based coupling through the outer ear canal. As a result, the method described below, in accordance with the present invention, presents a solution to the unmet need for a technique in the clinician's toolbox that can visually identify and quantitatively characterize a MEE, as well as assess the middle ear for infection noninvasively and in vivo.
The relation of diffusion to viscosity embodied by the Einstein-Stokes equation was first expressed in Einstein's 1905 Brownian motion paper. The use of DLS to derive the diffusion coefficient of particles in a fluid was pioneered by Willis H. Flygare, late professor of chemistry at the University of Illinois, and others, in the early 1970s.
Prior art examples of applying OCT to DLS may be found in Kalkman et al., “Path length resolved diffusive particle dynamics in spectral domain OCT,” Phys. Rev. Lett., vol. 105, 198302 (2010), Lee et al., “Dynamic light scattering optical coherence tomography,” Opt. Exp., vol. 20, pp. (2012), and in Kim et al., “Imaging and quantifying Brownian motion of micro-and nanoparticles using phase-resolved Doppler variance optical coherence tomography,” J. Biomed. Opt., vol. 18, 030504 (2013), all of which are incorporated herein by reference. DLS is a widely applied in many fields, including medicine and biophysics, and is used to determine the Stokes-Einstein (S-E) diffusion coefficient of particles undergoing Brownian motion by analyzing the intensity cross-correlation of the light scattered from the diffusing particles. Since the backscattering cross-section is the primary source of contrast in OCT, DLS measurements can be readily performed using OCT data.
One technique that uses Doppler variance rather than cross-correlation techniques may be found in Kim et al., “Imaging and quantifying Brownian motion of micro-and nanoparticles using phase-resolved Doppler variance optical coherence tomography,” J. Biomed. Opt., vol. 18, 030504 (2013), which is incorporated herein by reference. While Doppler variance is a scattering technique like that of the present invention, Doppler variance requires a flowing particle stream, whereas DLS does not.
OCT imaging of the middle ear has been the subject of various Boppart et al. presentations, publications and patents, such as Monroy et al, “Noninvasive depth-resolved optical measurements of the tympanic membrane and middle ear for differentiating otitis media,” The Laryngoscope, vol. 125, pp. E276-82. (2015), which is incorporated herein by reference.
Prior to the present invention, however, it was not known that particles in middle ear effusions and in other biofilms may be characterized in a manner that lends itself to OCT measurement of diffusion, and thus to derivation of a viscosity, based on OCT measurement, subject to a calibration. The inventions described herein, furthermore, reflect the recognition of the utility and the clinical application of OCT-based viscosity measurement to diagnosis of middle ear pathologies.